Hemodiafiltration combines both standard hemodialysis and hemofiltration into one process, whereby a dialyzer cartridge containing a high flux membrane is used to remove substances from the blood both by diffusion and by convection. The removal of substances by diffusion is accomplished by establishing a concentration gradient across a semipermeable membrane by flowing a dialysate solution on one side of the membrane while simultaneously flowing blood on the opposite side of the membrane. In existing systems, to enhance removal of substances using hemodiafiltration, a solution called substitution fluid is continuously added to the blood either prior to the dialyzer cartridge (pre-dilution) or after the dialyzer cartridge (post-dilution). An amount of fluid equal to that of the added substitution fluid is ultrafiltered across the dialyzer cartridge membrane carrying with it additional solutes.
Substitution fluid is usually purchased as a sterile/non-pyrogenic fluid contained in large flexible bags or is produced on-line by filtration of a non-sterile dialysate through a suitable filter cartridge rendering it sterile and non-pyrogenic. Techniques for online production of substitution fluid have been described in the literature, for example, in D. Limido et al., “Clinical Evaluation of AK-100 ULTRA for Predilution HF with On-Line Prepared Bicarbonate Substitution Fluid. Comparison with HD and Acetate Postdilution HF”, International Journal of Artificial Organs, Vol. 20, No. 3 (1997), pp. 153–157.
In general, existing hemodiafiltration schemes use a single dialyzer cartridge containing a high flux semi-permeable membrane, for example see P. Ahrenholz et al., “On-Line Hemodiafiltration with Pre- and Postdilution: A Comparison of Efficiency”, International Journal of Artificial Organs, Vol. 20, No. 2 (1997), pp. 81–90. In prior art systems, substitution fluid is introduced into the blood stream either in a pre-dilution mode or in a post-dilution mode relative to the dialyzer cartridge. The preferred mode for maximal removal of both small and large substances from blood, in accordance with the prior art, is the post-dilutional mode because this mode achieves the highest concentration gradient between the blood and the dialysate fluid. In a typical pre-dilution mode with on-line generation of substitution fluid, however, the bloodside concentration is lowered relative to the dialysate fluid. As a result, removal (or clearance) of substances can decrease, as described in The International Journal of Artificial Organs, 1997, vol. 20, pp. 81–90. This decrease is particularly apparent for smaller molecules, like urea, where mass transport is driven more by diffusion than by convection. Use of two dialyzer cartridges in a hemodiafiltration scheme has been reported in J. H. Miller et al., “Technical Aspects of High-Flux Hemodiafiltration for Adequate Short (Under 2 Hours) Treatment”, Transactions of the American Society Artificial Internal Organs (1984), pp. 377–380. In this scheme, the substitution fluid is reverse-filtered through the membrane of the second dialyzer cartridge simultaneously with the filtration of fluid across the membrane of the first dialyzer cartridge. A variation of this method is described in B. Nederlof, “HEMO(DIA)FILTRATION APPARATUS AND FILTRATE FLOW REGULATOR”, U.S. Pat. No. 5,600,722 (1997), wherein a dialysate pump between the dialyzers is used to regulate the amount of reverse-filtration in the second dialyzer cartridge. Another two cartridge system is described in P. Ghezzi et al., “BLOOD PURIFYING EQUIPMENT PARTICULARLY FOR THE TREATMENT OF PATIENTS SUFFERING FROM RENAL INSUFFICIENCY, AND A METHOD OF PRODUCING A REINFUSION LIQUID FOR Hemodiafiltration (HDF)”, U.S. Pat. No. 5,194,157 (1993). In this patent, blood flows through a first filter cartridge whereby plasma water is filtered across a semi-permeable membrane as a means to remove blood substances by convection. A process, such as adsorption, is then performed on a portion of the filtered plasma water to produce an infusion fluid that is reintroduced back into the blood stream. The filtered blood then passes through a dialyzer cartridge containing a semi-permeable membrane whereby removal of blood substances occurs by diffusion into a dialysate fluid stream. Thus, blood is subjected to a hemofiltration process in a first cartridge stage followed by a hemodialysis process in a second cartridge stage.
Certain trade-offs exist with respect to removal of different size molecules when comparing pre-dilution hemodiafiltration and post-dilution hemodiafiltration using a single dialyzer cartridge. For example, on-line pre-dilution hemodiafiltration schemes generally achieve higher convection filtration rates, compared to on-line post-dilution hemodiafiltration, enhancing removal of large molecules; however, the increased removal by convection comes at the expense of reducing the removal of small molecules, such as urea and creatinine. In on-line post-dilution hemodiafiltration schemes, on the other hand, the amount of fluid that may be filtered from the blood as it passes through the dialyzer cartridge is limited. Specifically, the filterable amount is dependent upon several factors, which include blood flow rate, blood hematocrit, and blood protein concentration. Typically, the filterable amount is 20% to 30% of the incoming blood flow rate. For example, at a blood flow rate of 300 milliliter per minute (ml/min), the filterable amount is typically limited to 90 ml/min. In the two dialyzer approach described by J. H. Miller et al., the filterable amount is also limited to about 20% to 30% of the blood flow because forward filtration occurs only in the first dialyzer. The second dialyzer then re-infuses the fluid lost in the first dialyzer by reverse-filtration, as in on-line post-dilution hemodiafiltration. In the approach described by P. Ghezzi et al., the filterable amount is also limited to about 20% to 30% of the blood flow because forward filtration occurs only in the first hemofilter cartridge.